Investigational Tx May Stop MS Symptoms Long-Term, but It's Risky

The researchers destroyed the immune system of the patients before stem cell transplantation
The researchers destroyed the immune system of the patients before stem cell transplantation

An investigational multiple sclerosis (MS) treatment demonstrated the ability to stop relapses and new brain lesion development for a prolonged period without the need for ongoing medication, in a new phase 2 clinical trial.

Researchers from The Ottawa Hospital and the University of Ottawa, Canada, experimented with a variation of the autologous hematopoietic stem cell transplantation (aHSCT) method. Typically this method involves harvesting bone marrow stem cells from a patient, using chemotherapy to suppress the immune system, and then finally reintroducing the stem cells to ‘reset' the immune system from attacking the body. However, it is not always successful with many patients regularly relapsing afterward. 

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In this trial, instead of merely suppressing the immune system before transplantation, the researchers completely destroyed it using a chemotherapy regimen of busulfan, cyclophosphamide and rabbit anti-thymocyte globulin.

Twenty-four patients aged 18–50, whose MS was not controlled by immunosuppressive therapy, were enrolled in the study. The patient's disabilities, as defined by the Expanded Disability Status Scale (EDSS) scores, ranged from moderate to requiring a walking aid to walk 100m. The primary endpoint of the trial was activity-free survival at 3 years.

In the majority, results were positive, though one patient died from hepatic necrosis and sepsis due to the chemotherapy. Among the other 23 patients, none experienced a relapse during the follow up period (between 4 to 13 years). Before the treatment, patients were experiencing an average of 1.2 relapses a year. 

Of the 327 total brain scans during follow-up, just one scan identified a new lesion. The study results showed additional benefits: progressive brain deterioration decreased to the rate associated with normal aging in 9 patients; 8 patients showed sustained improvement in their EDSS score at 7.5 years after treatment; and 6 returned to work or school and stopped receiving disability insurance 3 years after treatment. Moderate and mild toxic effects were reported in 8 and 14 of the patients, respectively.

The authors noted the limitations to their study, including the low sample size (N=24) and lack of control group. “Larger clinical trials will be important to confirm these results,” said co-lead author, Dr. Mark S Freedman.  “Future research will be directed at reducing the risks of this treatment as well as understanding which patients would best benefit from the treatment.”

Dr. Jan Dörr, from the NeuroCure Clinical Research Center, Berlin, Germany, expressed his approval of the study, “This trial is the first to show complete suppression of any inflammatory disease activity in every patient for a long period.” However he also cautions about the low safety profile, but acknowledged that the treatment could be justified for some. “[…] There may be support for considering aHSCT less as a rescue therapy and more as a general treatment option, provided the different protocols are harmonized and optimized, the tolerability and safety profile can be further improved.”

For more information visit TheLancet.com.

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